Antigens expressed by endocrine pancreatic islet cells play important roles in the immune recognition, autoimmunity and beta cell destruction of Type I diabetes mellitus. In addition, these unique islet cell molecules are also involved in the many specialized functions of islet cells, like recognition of and binding to secretagogues, signal transduction and hormone secretion. Over the last two years, generation of monoclonal antibody probes has allowed me to identify and characterize several novel protein, glycoprotein and glycolipid islet cell antigens. Preliminary studies have suggested potential roles for these cellular differentiation antigens in islet cell autoimmunity and endocrine function. In this research proposal, through the combined use of "hybridoma" and recombinant DNA techniques I plan to, 1) isolate and affinity purify the monoclonal antibody defined islet cell antigens, 2) isolate and clone the genes encoding the islet cell proteins of interest, and 3) analyze their structure and examine at the cellular and molecular levels their roles in islet cell autoimmunity and islet endocrine function.